XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Lectures
MYCOBaCTErial maNNOSYL traNSferaSE PIMa as a TarGET for
THE DEvELOPMENT of NEW aNTITUBErCULar drUGS
Zuzana Svetlíková 1 , Marcelo E. Guerin 2 , Mary Jackson 3 ,
Jana Korduláková 1 and Katarína Mikušová 1
1
Comenius University, Faculty of Natural Sciences, Bratislava, Slovakia;
2
University of the Basque Country, Unit of Biophysics, Bilbao, Spain;
3
Colorado State University, Department of Microbiology, Immunology and Pathology,
Fort Collins, USA
Tuberculosis still remains one of the most serious infectious diseases in the world with
several million new cases each year. At present there are more than 2 billion people
infected with Mycobacterium tuberculosis, the causative agent of tuberculosis, with
a chance of one in ten for the development of the active disease. Increased prevalence
of multidrug-resistant and extensively drug-resistant strains of M. tuberculosis diminishes
the number of effective drugs available for the treatment of infections they cause. For
this reason there is a need for drugs with new mode of action. The unique mycobacterial
cell envelope provides an array of novel drug targets since its integrity is necessary
for bacterial viability. Phosphatidylinositol mannosides (PIM) are important part of this
crucial structure. They appear to be involved in host-pathogen interactions and serve as
a basis for the biosynthesis of other key molecules - mycobacterial lipopolysaccharides
lipoarabinomannan and lipomannan. Build up of PIM is initiated by the action of mannosyl
transferase PimA catalyzing the transfer of the mannose residue from GDP-mannose to
phosphatidylinositol. Since the reaction is essential for survival of M. tuberculosis, PimA
represents an attractive target for the drug development.
Acknowledgment: This work was supported by European Comission under contract
LSHP-CT-2005-018923”NM4TB“
100 XXII. Biochemistry Congress, Martin